Biomedical subjects
G A Klassen
Publications and source records attributed to G A Klassen.
Regional myocardial deoxyglucose uptake following electrical stimulation of canine efferent sympathetic cardiopulmonary nerves.
OBJECTIVE: The aim was to study the effect of stimulating individual acutely decentralised cardiopulmonary nerves on myocardial uptake of deoxyglucose. METHODS: In 17 open chest anaesthetised dogs the efferent axons of individual decentralised cardiopulmonary nerves were stimulated intermittently throughout 1 h while haemodynamic variables were measured. Tritiated 2-deoxyglucose was injected intravenously at the beginning of stimulation. Atropine was given when a cardiopulmonary nerve with efferent parasympathetic axons was studied. Distribution of label was detected using a multiwire proportional chamber. It was compared to blood concentration of deoxyglucose to permit quantitative mapping of regional myocardial uptake during the stimulation of each nerve. RESULTS: Neural stimulation of most of sympathetic efferent cardiopulmonary nerves increased deoxyglucose uptake in all myocardial tissue. Uptake was greatest in the left ventricle, less in the right ventricle, and least in the left and right atria. Regional myocardial uptake was also observed following individual cardiopulmonary nerve stimulation. Some nerves caused greater uptake than others. Cardiopulmonary nerves which are known to enhance inotropism when stimulated induced little increase of deoxyglucose uptake, whereas other nerves known to exert little positive inotropic effect induced considerable uptake. There was no correlation between haemodynamic changes and deoxyglucose uptake. CONCLUSIONS: It appears that (1) efferent sympathetic axons in one cardiopulmonary nerve can preferentially increase deoxyglucose uptake in specific regions of the myocardium and (2) the mechanisms responsible for enhancement of glucose uptake may differ from those responsible for inotropic responses.
A mouse model of coxsackievirus myocarditis.
OBJECTIVE: To develop a mouse model of coxsackievirus B3 (CVB3) myocarditis. DESIGN: Preliminary studies have indicated that mice infected with CVB3 alone erratically responded with viral myocarditis. Prospective evaluation of the effect of cyclophosphamide at two time intervals resulted in consistency for the development of myocarditis. ANIMALS: Juvenile five- to nine-week-old male mice CD-1 type (Charles River Canada Limited). INTERVENTIONS: Infection with coxsackie B3 enterovirus. Pretreatment with cyclophosphamide two days and 4 h before inoculation of 0.2 or 0.15 mg/g. Animals were killed seven, nine, 28 and 63 days post infection. MAIN RESULTS: Following cyclophosphamide conditioning, a tissue response infection with CVB3 was uniformly observed. Virus, however, was infrequently recovered from the myocardium whereas myocarditis became chronic after 28 days. CONCLUSIONS: Pretreatment of juvenile mice with cyclophosphamide results in a reproducible model of viral myocarditis with chronic changes in the myocardium.
Focal myocardial necrosis associated with multiple sclerosis of the medulla.
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Stability of diltiazem and its metabolites in plasma during storage.
Diltiazem (DTZ) is a calcium antagonist widely used in the treatment of angina and related heart diseases. It is extensively metabolized into a host of metabolites, some of which have potent pharmacological activities. Previous work has shown that DTZ and its major metabolite N-desmethyl-DTZ (MA) were unstable and readily decomposed to deacetyl-DTZ (M1) and deacetyl N-desmethyl-DTZ (M2), respectively. This report describes the stability of DTZ and its metabolites in plasma samples stored at -20 and -70 degrees C for different periods up to 12 weeks. The results indicate that in those samples obtained from volunteers who received DTZ, no deterioration of DTZ or MA occurred up to 8 weeks, but considerable deterioration of DTZ to M1 and MA to M2 (p less than 0.01) occurred after 12 weeks. However, in samples prepared by adding DTZ and its metabolites to outdated plasma (spiked plasma), deterioration of DTZ occurred after 4-6 weeks of storage, but there were no concomitant increases in concentrations of M1 or M2. Thus, it appears that decomposition of DTZ and MA was affected by the nature of the plasma materials, but the reason for the differences in analyte stability observed between volunteers' and spiked plasma is not known. Also, it appeared that DTZ and its metabolites in plasma samples stored at -70 degrees C may be more stable than those at -20 degrees C, although further studies are required to substantiate this observation. On the basis of these results, plasma samples obtained from patients or volunteers receiving DTZ should be analyzed within 8 weeks when the samples are stored frozen at -20 degrees C.
Effect of diltiazem and its metabolites on the uptake of adenosine in blood: an in-vitro investigation.
Using whole blood from man and rabbits, the effect of diltiazem, its metabolites, and other calcium antagonists on the uptake of adenosine has been described. The uptake and metabolism of adenosine was extremely rapid with a half-life in plasma of less than 30 s. Adenosine is rapidly and extensively metabolized to hypoxanthine. Metabolites of diltiazem, deacetyl diltiazem and deacetyl O-desmethyl diltiazem were considerably more potent than the parent drug. Diltiazem was one-tenth as active as verapamil, but more active than nifedipine or amlodipine. Dipyridamole was the most potent uptake-inhibitor tested (IC50 less than 1 microM), whereas the angiotensin converting enzyme inhibitor enalapril was virtually devoid of any inhibitory activities (IC50 greater than 1000 microM). The results obtained from both man and rabbit were similar.
Effects of increasing heart rate induced by efferent sympathetic neuronal stimulation, isoproterenol or cardiac pacing on myocardial function and oxygen utilization.
The effects of increasing heart rate by six different methods on cardiac function were investigated in 17 open-chest anesthetized dogs. Heart rate was increased approximately 30% by (1) right interganglionic nerve stimulation, (2) atrial pacing, (3) ventricular pacing, (4) atrioventricular sequential pacing, (5) right stellate ganglion stimulation, and (6) isoproterenol administration. During heart rate increases induced by atrial pacing left ventricular intramyocardial pressure, coronary blood flow, oxygen delivery per unit of myocardial oxygen consumption, and myocardial efficiency were unchanged. Ventricular pacing reduced left ventricular cavity and septal intramyocardial pressure, while circumflex coronary flow increased, resulting in reduced oxygen delivery relative to myocardial oxygen consumption. Similarly, atrioventricular sequential pacing increased circumflex coronary artery flow and myocardial oxygen consumption, and decreased septal intramyocardial pressure and oxygen delivery per unit of myocardial oxygen consumption. Right stellate ganglion stimulation and isoproterenol increased left anterior descending and circumflex coronary artery blood flow, intramyocardial pressure, and myocardial oxygen consumption. Estimated myocardial efficiency (left ventricle) was decreased by ventricular pacing and isoproterenol, and was unchanged by atrial pacing and right interganglionic nerve stimulation. Increases in heart rate induced by right interganglionic nerve stimulation did not alter myocardial oxygen consumption, or the index of cardiac efficiency. It is concluded that augmentation of heart rate by either ventricular or atrioventricular pacing impairs myocardial function so that there is a decrease of left ventricular efficiency and isoproterenol augments chronotropism and myocardial force relative to cardiac external work so there is a reduction in cardiac efficiency. In contrast, atrial pacing or right interganglionic nerve stimulation augments chronotropism such that myocardial oxygen consumption and efficiency are unchanged.
Hemodynamic monitoring of the acutely ill patient.
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Autoimmune myocarditis: a clinical entity.
In a case of myocarditis electron microscopic and immunoflourescent studies of a transmural myocardial biopsy specimen indicated an autoimmune process. Extensive inflammatory cell infiltration, immunoglobulin and complement deposition along the sarcolemma and in the interstitium, and capillary endothelial injury were found. After a short course of immunosuppressive therapy the inflammatory process was replaced by collagenous scarring and lymphocytic depletion; the blood vessels were then normal. Earlier therapy in such cases may be lifesaving.
The effect of myocardial force on coronary transmural flow distribution.
The role of myocardial force as a determinant of transmural coronary flow distribution was examined in the presence and absence of autoregulation by infusing calcium chloride into a segment of the left coronary system. The concentration of calcium used was adequate to increase force but did not alter coronary pressure or endoventricular pressure. No alterations in transmural gradients of flow were observed following increased regional force. These results suggest that increases in regional force are not of importance as a determinant of transmural blood flow.
A variable criterion circuit for biofeedback training.
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Redistribution in left ventricular regional flow following acute right ventricular pressure overload.
The left ventricular dysfunction following acute pulmowary hypertension remains unexplained. We wondered if acute pulmonary hypertension could alter the transmural flow distribution within the left ventricular myocardium, independent of coronary flow and perfusion pressure. We used a canine preparation in which the left coronary system was perfused at constant flow and induced a two- to three-fold increase in pulmonary artery pressure by banding the pulmonary artery. Regional myocardial blood flow of the left coronary system was measured using radioactive microspheres, injected into the left coronary system before and after 10-30 min of banding of the pulmonary artery. The left ventricular subendocardial:epicardial ratio fell by 12 and 31% (p less than 0.05) of control value, 10 and 30 min, respectively, after banding of the pulmonary artery, the total flow to the left coronary system being kept constant. Left atrial mean pressure increased from 2.9 +/- 2.4 to 3.6 +/- 1.9 and 6.0 +/- 2.1 (p less than 0.05) following banding. The mechanism of the redistribution of coronary flow may relate to inappropriate vasodilation of the right septal myocardium with consequent relative left ventricular subendocardial hypoperfusion which might aggravate left ventricular ischemia in the presence of hypotension and hypoxia.
Autoregulation of cerebral blood flow during early experimental renal hypertension in the conscious dog.
Using the radioactive microsphere technique, cerebral blood flow (CBF) was measured in six conscious dogs before intervention and again on the 3rd-5th days after inducing hypertension by the one-kidney Goldblatt (1-KGH) procedure. Sham-operated controls were also studied. The normal temporal variability of CBF, as well as the precision of the microsphere technique in measuring CBF were also determined in other normal dogs. A left atrial catheter was used for the microsphere injections (15 micrometer diam spheres) and an aortic catheter was used for cardiac output and blood pressure measurements. On the 3rd-5th days after 1-KGH, mean aortic pressure increased from a control value of 94 +/- 7 mmHg to 135 +/- 20 mmHg (P less than 0.005). CBF did not change significantly from the control flow of 57.1 +/- 7.9 ml/100 g per min. Calculated cerebral vascular resistance increased by 47 percent (P less than 0.025) above the control value. Hence, the early phase of experimental renal hypertension is associated with adequate autoregulation of cerebral blood flow.
Role of autoregulation in spatial and temporal perfusion heterogeneity of canine myocardium.
Spatial heterogeneity, the region-to-region variation in flow at an instant, and temporal heterogeneity, the time variation of flow in a small region of myocardium, were investigated with radioactive labeled microspheres in 111 regions of left ventricular myocardium. The error of the method was measured by simultaneously injecting four differently labeled microspheres (15 +/- 5 (SD) micron). The coefficient of variation (CV) was 6.5 +/- 1.0%. Spatial variation with autoregulation intact was 21.7 +/- 1.4% (CV); with autoregulation abolished and low perfusion pressure, it was 34.3 +/- 3.7%; and with normal perfusion pressure, 30.8 +/- 6.4% (differences not significantly). This degree of variation was similar in the entire left ventricle and its layers. Forces which tended to cause vessel closure (low perfusion pressure, ventricular systolic pressure, and ventricular diastolic pressure) tended to increase CV. Temporal heterogeneity as measured by 20-s intervals between microsphere injections was 11.1 +/- 1.0% (CV) with autoregulation, 9.8 +/- 1.3% (P less than 0.05) with autoregulation abolished, and 8.4 +/- 0.8% (P less than 0.05) when perfusion pressure was restored. A periodicity of flow cycles of 30-90 s was suggested by the data. These results suggest that spatial heterogeneity is less influenced by autoregulation than by hydraulic considerations, whereas temporal heterogeneity is a component of autoregulation.
Transmural myocardial deformation in the canine left ventricular wall.
A biplane cineradiographic technique was used to measure deformation of the myocardium as indicated by small lead spheres implanted into the anterior left ventricular wall of anesthetized dogs. Deformation was resolved into nine separate components for each of the epicardial, middle, and endocardial layers. The data illustrate the mechanical effect of myocardial fiber orientation and the ability of muscle layers to deform differentially. In order to present an overview of all the results, the implications of the deformation components are discussed first separately and then in a coordinated fashion.
The determinants of regional myocardial blood flow.
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Myocardial infarction after aortocoronary saphenous vein bypass. Vectorcardiographic study.
Vectorcardiograms and scalar electrocardiograms were recorded in 30 patients before and after aortocoronary saphenous vein bypass surgery to determine whether vectorcardiograms are helpful in making the diagnosis of perioperative transmural infarction. The vectorcardiogram indicated inferior infarction in 2 cases and anterior infarction in 1 case when the diagnosis was not apparent on the electrocardiogram. In the solitary case of anterior infarction diagnosed by the electrocardiogram, anterior infarction was already present on the preoperative vectorcardiogram. The study indicates that the recording of vectorcardiograms before and after aortocoronary bypass surgery facilitates the diagnosis of perioperative anterior and inferior infarction and may reveal perioperative infarction about a previously infarcted area.
The role of coronary flow and pressure as determinants of myocardial oxygen consumption in the presence or absence of vasomotor tone.
When coronary flow was kept constant and coronary pressure increased by angiotensin or decreased by dipyridamole, myocardial oxygen consumption (MVO2) remained unchanged. When vasomotor tone was abolished by dipyridamole or was intact, changing coronary flow resulted in a change in MVO2 in the same direction as flow; this change in MVO2 was in part the result of a significant alteration in coronary oxygen extraction. These results suggest that coronary flow, but not coronary pressure is an important determinant of MVO2 both in the presence or absence of vasomotor tone.